Members of the pentraxin family, including PTX3 and serum amyloid P component (SAP), have been reported to play a role in innate host defence against a range of microbial pathogens, yet little is known regarding their antiviral activities. In this study, we demonstrate that human SAP binds to human influenza A virus (IAV) strains and mediates a range of antiviral activities, including inhibition of IAV-induced hemagglutination (HA), neutralization of virus infectivity and inhibition of the enzymatic activity of the viral neuraminidase (NA). Characterization of the anti-IAV activity of SAP after periodate or bacterial sialidase treatment demonstrated that α(2,6)-linked sialic acid residues on the glycosidic moiety of SAP are critical for recognition by the HA of susceptible IAV strains. Other proteins of the innate immune system, namely human surfactant protein A and porcine surfactant protein D, have been reported to express sialylated glycans which facilitate inhibition of particular IAV strains, yet the specific viral determinants for recognition of these inhibitors have not been defined. Herein, we have selected virus mutants in the presence of human SAP and identified specific residues in the receptor-binding pocket of the viral HA which are critical for recognition and therefore susceptibility to the antiviral activities of SAP. Given the widespread expression of α(2,6)-linked sialic acid in the human respiratory tract, we propose that SAP may act as an effective receptor mimic to limit IAV infection of airway epithelial cells.

We conducted a systematic review and a fixed-effects meta-analysis to determine whether incident adverse psychiatric events (APE) including depression, anxiety, psychosis, or suicide were associated with biologic therapy in IBD. Six randomized controlled trials and a cohort study met criteria, reporting an incidence of APE in 4,882 patients. The risk difference per 100 person-months of any APE with a biologic medication was 0.01 (95% confidence interval = 0.00-0.02). There was insufficient evidence available in randomized controlled trials to conclude that biologic therapy in IBD is associated with an increased incidence of APE.

NCT00336336 (GISSI-HF), NCT00206310 (CORONA).

Registries are an important platform to which persons with dementia and other cognitive impairments can contribute to research studies. Registries also provide an opportunity for patients to stay informed about current studies. Engaging patients in registry development can increase sustainability of a registry and patient retention in clinical registries. We sought the perspective of persons with dementia and their accompanying family members about their registry participation experiences, barriers and facilitators to participation, and potential avenues for improvement of registry processes such as recruitment, data collection, and knowledge translation. Two semi-structured focus groups with persons with dementia and their family members (<i>n</i> = 18) were conducted and analyzed using thematic content analysis. Participants were recruited from an existing patient registry made up of patients currently being seen in a dementia assessment clinic. The main themes identified included altruistic motives with regards to registry participation; and access to and privacy of personal health information. As electronic health records are becoming more common, understanding barriers and facilitators from the perspectives of people with dementia is essential to inform the future development of cognitive condition-related registries. The results from our focus groups identified engagement strategies and solutions to overcome perceived barriers for individuals experiencing progressive cognitive decline to participate in longitudinal registry projects.

Abstract Immune system plays a dual role in cancer development and progression. Under conditions of chronic inflammation the repair response initiated by the immune system strongly promotes tumor growth. Epidemiological evidence of increased cancer incidence in organ transplant recipients and immune compromised individuals suggests a critical role for immune surveillance in keeping cancer under control. The cellular and molecular mechanisms that control tumor promoting chronic inflammation or tumor suppressing immune surveillance are unclear. Chemokines direct the migration of leukocytes to the sites of infection or injury and therefore are likely to play a central role in perpetuating tumor promoting chronic inflammation as well as orchestrating tumor eradicating immune surveillance. D6 is a chemokine decoy receptor and an effective scavenger of inflammatory CC-chemokines. D6-knockout (D6-/-) mice showed enhanced inflammation in different models including carcinogen-induced inflammation-promoted skin cancers. In this study, we show that D6-/- mice when bred onto mice with a heterozygous mutation in the adenomatous polyposis coli (ApcMin/+) gene demonstrated reduced intestinal tumor burden and increased survival. A decrease in tumor promoting inflammation is coincidental with increased mast cells and CD8+ T cell activation profiles in tumors from the D6-/-ApcMin/+ mice compared to ApcMin/+ mice. The D6-/-ApcMin/+ mice in the context of the lymphocyte deficient, Rag2-/-background (Rag2-/-D6-/-ApcMin/+), showed a significant increase in tumor burden that is reversed by the adoptively transferred CD8+ and/or CD4+T-lymphocytes from the D6-/-ApcMin/+ mice. Chemokine levels in serum and chemokine receptor expression patterns on lymphocytes from the ApcMin/+ and D6-/-ApcMin/+ mice and the Rag2-/-D6-/-ApcMin/+ mice undergoing adoptive transfer treatments identified the increased levels of ligand-receptor pairs of LTB4/BLT1, CCL2/CCR2, and CXCL9/CXCR3 being critical in promoting tumor suppressive immune surveillance in this spontaneous tumor model. These results show that inflammatory chemokines play a protective role against progression of intestinal cancers by immune surveillance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 800. doi:10.1158/1538-7445.AM2011-800

There was no funding for this study.